Immune system holds cancer dormant

“Millions of cancer patients could be given the power to ‘control’ the disease after a major breakthrough by scientists,” reported the Daily Mail today.

The report continued that scientists have shown “that the body's immune system can keep tumours dormant for years without them becoming dangerous”. This finding could lead to treatments for cancer sufferers, allowing them to live with “neutralised” cancers that are unable to grow and cause further damage.

The newspaper report is based on a laboratory study conducted in mice. Although the findings are exciting for the scientific community, further studies are needed to see what they mean for human health and how they will translate into specific cancer treatments. It can take decades for an initial scientific finding to develop so that it can be applied to the treatment of humans.

Where did the story come from?

Dr Catherine Koebel and colleagues from Washington University School of Medicine and other academic and medical institutions in the USA carried out this study. The research was supported by grants from the National Cancer Institute, the Ludwig Institute for Cancer Research, and the Cancer Research Institute. The study was published in the peer-reviewed medical journal: Nature.

What kind of scientific study was this?

This was a laboratory study conducted in several different types of mice; including two common strains of laboratory mice and a breed of genetically modified mice bred with an immune system that had no ability to recognise and remember invading cells.

The different strains were used in different aspects of the study, which together, investigated the characteristics of tumour cells that are being held dormant, and particularly those tumours which have been dormant for some time then later develop into cancer.

In their initial experiment, the researchers injected a strain of mice commonly used for laboratory studies with a chemical known to cause cancer (MCA – methylcholanthrene). They then monitored the mice for about 200 days to see whether any tumours developed. Mice that showed actively growing tumours were removed from the study, while mice which had small, stable tumours around the site of the MCA injection, and mice without any tumours were kept in the study.

The remaining mice were then given weekly injections of one of two types of monoclonal antibody (antibodies which can bind to specific cells); one that reduced the functioning of specific parts of the immune system and one that had no effect on that part of the immune system (a placebo).

Both groups were then monitored for a further 100 days for tumour development. This allowed the researchers to compare the effects that modifying the immune system in this way had on development or growth of cancer cells.

The researchers conducted similar experiments in a different strain of laboratory mice and chemically suppressed different parts of the mice immune system. This allowed the researchers to explore which elements of the immune system were helping the body to prevent the cancer cells from growing, i.e. maintaining them in a dormant state.

To further explore the role of the immune system, researchers repeated the experiments in genetically modified mice that had greatly reduced adaptive immunity (the immune system’s ability to recognise and remember invading cells).

They also dissected out the tumours that had formed in most mice at the site of their MCA injection and examined them microscopically.

What were the results of the study?

In their initial experiment, the researchers found that none of the mice given the placebo (i.e. those whose immune functioning was not altered) developed additional tumours while nine of the 15 mice (60%) whose immunity had been altered developed rapidly growing sarcomas (a type of cancerous tumour). Similar results were found when the study was repeated across different laboratories and using different strains of mice.

The researchers found that suppressing the part of the immune system responsible for adaptive immunity resulted in late development of rapidly growing cancers. In genetically modified mice that essentially had no functioning adaptive immune system, tumours developed very quickly, i.e. there were no late growing tumours. This suggests that the adaptive immune function can delay tumour growth and without it, tumours grow quickly.

Examination of the dissected stable tumours (i.e. the tumours that were seen in the mice but that were being prevented somehow from growing rapidly) revealed that they were somehow being programmed to kill themselves and not to replicate. When these stable tumours were transplanted into mice that had malfunctioning immunity, they grew into serious cancers. This showed that something specific to the host’s immunity was keeping them in check.

What interpretations did the researchers draw from these results?

The researchers conclude that their study has highlighted the body’s capacity to control cancer for “long periods by a process called equilibrium”. They have shown that cells that are held in a dormant state appear to be capable of inducing an immune response while those that escape from this state are not so easily controlled by the body.

They suggest that many tumours may progress through different states, firstly where some of the cancer cells are eliminated early by the body, secondly where some cells are held in an equilibrium state (stable tumours) and finally where cells escape from the equilibrium and develop rapidly into cancer).

What does the NHS Knowledge Service make of this study?

This study has shown that immunity can influence the development of cancer in mice. At present, the findings of this complex laboratory study have the most relevance for clinical scientists, rather than health professionals or patients.

Though the researchers acknowledge that their study was done in an animal model of cancer, they think that it is relevant for humans for the following reasons:

a possible goal of treatment in future may be to maintain cancer cells in this “stable” state by enhancing the activity of the adaptive immune system

the findings shed light on the fact that some tumours never lead to clinical symptoms of disease

the findings put forward one explanation why cancer can develop after an organ transplantation where the host didn’t have cancer

The researchers say that their results “provide a foundation for future work to define the molecular mechanisms by which adaptive immunity maintains cancer in a dormant state”.

Although this well conducted research will gain a lot of attention from the scientific community, at this early stage it is unclear how the findings will translate into human treatments. It typically takes decades for an initial scientific finding to reach a point where it can be applied to human therapy.